Condition category
Circulatory System
Date applied
30/09/2005
Date assigned
30/09/2005
Last edited
17/04/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Morris J Brown

ORCID ID

Contact details

Box No 110
Dept. of Clinical Pharmacology
Addenbrooke's NHS Trust
Cambridge
CB2 2QQ
United Kingdom
+44 (0)1223 762574
mjb14@medschl.cam.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0544160627

Study information

Scientific title

Acronym

Study hypothesis

Can the oral glucose tolerance test detect changes after 4 weeks treatment with thiazide diuretics or beta blockers or combination of the two?

Ethics approval

Added 5 August 2008: approved by Cambridge Research Ethics Committee on
26/11/04.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Hypertension

Intervention

Drug(s) vs placebo.
Blood samples for glucose and insulin determination. Collected by Research team/CIW staff.

Intervention type

Drug

Phase

Not Specified

Drug names

Atenolol, bendrofluazide

Primary outcome measures

Change in 2 hour glucose between any drug/drug combination versus placebo.

Secondary outcome measures

Added 5 August 2008:
1. Do patients show a similar change in glucose tolerance after thiazide or
beta blocker treatment?
2. Does the combination of drugs cause a greater reduction in glucose tolerance
than expected from the response to each drug alone?

Overall trial start date

01/02/2005

Overall trial end date

01/02/2008

Reason abandoned

Eligibility

Participant inclusion criteria

Non-diabetic patients who are diagnosed as having essential hypertension will be recruited.

We will be comparing the two most commonly used drugs to treat hypertension, atenolol and bendrofluazide, in patients for whom the drugs (and the doses to be used) are licenced.

We propose an initial open label pilot study of 10-12 patients to confirm final doses to be tested, the duration of therapy for optimum timing of the OGTT and tolerability of doses selected. The pilot study will also be used to confirm sample size calculations for the main study. The protocol for the pilot study will be identical to the main study, but there will not be a placebo phase and the treatment will not be blinded.

The main study will be double-blind, placebo controlled, cross-over study, of approximately 66 patients in which each patient receives in random order, 4 weeks treatment with either Bendrofluazide 5-10mg daily, Atenolol 50-100mg daily or combination of Bendrofluazide 2.5-5mg and Atenolol 25-50mg daily. There will be a forced titration from the lower to the higher dose stated half way through each dosing period. There will be a 1 month placebo wash-out between each dosing period.

At 0, 2 and 4 weeks of each treatment phase, patients will attend the Clinical Investigation Ward (CIW), fasting, for performance of an oral glucose tolerance test (OGTT). Blood will be drawn from an intravenous cannula, for the measurements of glucose and insulin at 0, 1 and 2 hours.

Blood pressure will be measured at each study visit using an Omron machine. The patients will also be given a blood pressure machine to take home and will be asked to measure and record their blood pressure at least twice per week. If their blood pressure is under 110/70mmhg or over 160/110mmHg at any time or if the patient has symptoms e.g. headache or dizziness, the patient will be asked to contact study staff. If the blood pressure remains over 160/110 for two measurements, then another antihypertensive therapy may be commenced, or the patient withdrawn from the study. If blood pressure is < 110/70 mmHg with symptoms then a decision may be made to terminate their participation in the study.

The doses of drugs to be used, while commonly used for angina and oedema, are higher than now commonly used for hypertension. We expect them to be well tolerated during short term use. These doses have also been chosen because they will enable genetic studies top be performed subsequently in a large number of patients.

Prof M Brown and Clinical Pharmacology Unit team has experience of many research studies in the treatment of hypertension. The design of this study has been derived partly from previous experience from these studies and from patient suggestions from these studies.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Pilot: 12, main study: 66

Participant exclusion criteria

1. Any patient already taking thiazide diuretics or beta blockers in whom these drugs cannot be switched to alternative drugs with similar or better blood pressure control.
2. Any patient who is intolerant of these medications will be excluded from the study.

Recruitment start date

01/02/2005

Recruitment end date

01/02/2008

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Box No 110
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Organisation

Department of Health

Sponsor details

Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk

Sponsor type

Government

Website

http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Government

Funder name

Cambridge Consortium - Addenbrooke's (UK) - NHS Research and Development Support Funding

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22493073

Publication citations

  1. Results

    Stears AJ, Woods SH, Watts MM, Burton TJ, Graggaber J, Mir FA, Brown MJ, A double-blind, placebo-controlled, crossover trial comparing the effects of amiloride and hydrochlorothiazide on glucose tolerance in patients with essential hypertension., Hypertension, 2012, 59, 5, 934-942, doi: 10.1161/HYPERTENSIONAHA.111.189381.

Additional files

Editorial Notes